...Diversity of microbial growth strategies in a limited nutrient world Saccharomyces cerevisiae is a prime organis...Now scientists from New York University have now developed a sophisti...The researchers studied growth rates and lag times in both lab strains...

The budding yeast, Saccharomyces cerevisiae, is a prime organism for studying fundamental cellular processes, with the functions of many proteins important in the cell cycle and signaling networks found in human biology having first been discovered in yeast.

Now, scientists from New York University have now developed a sophisticated assay to track cell growth at very low nutrient concentrations. The assay uses time-lapse microscopy to monitor individual yeast cells undergoing a small number of divisions to form microcolonies. The assay can measure the lag times and growth rates of as many as 80,000 individual microcolonies in a single 24-hour experiment, opening up a powerful new high-throughput tool to study the complex interplay between cell growth, division and metabolism under environmental conditions that are likely to be ecologically relevant but had previously been difficult to study in the laboratory.

The researchers studied growth rates and lag times in both lab strains and wild yeast by varying the amount of its prime carbon food source, glucose. They confirmed the prediction made over 60 years ago by Noble-prize-winning biologist Jacques Monod regarding changes in microbial growth rates with limited nutrients (the Monod equation). They also found significant differences among strains in both the average lag response (the amount of time it takes to transition from cell quiescence to restarting cell growth) and average growth rates in response to different environmental conditions.

In addition to average differences between strains and conditions, the powerful assay revealed metabolic differences among cells of the same strain in the same environment. Moreover, yeast strains differed in their variances in growth rate. According to the study's lead author, Naomi Ziv, "Heterogeneity among genetically identical cells in the same environment is a topic of increasing interest in biology and medicine. The different strain variances we see suggest that the extent of nongenetic heterogeneity is itself genetically determined."

Further investigations could pave the way to a more complete understanding of the genetics and metabolomics of cell growth in yeast and the underlying mechanisms relevant to other settings in which cells face challenging conditions, such as cancer progression and the evolution of drug resistance.

David Gresham
Center for Genomics and Systems Biology
Department of Biology
New York University,
New York, USA
dgresham@nyu.edu

Mark L. Siegal
Center for Genomics and Systems Biology
Department of Biology
New York University,
New York, USA
mark.siegal@nyu.edu

Examining the source behind Sherpa mountain fitness

The Sherpa population in Tibet is world-renowned for their extraordinary high-altitude fitness, as most famously demonstrated by Tenzing Norgay's ability to conquer Mount Everest alongside Sir Edmund Hillary. The genetic adaptation behind this fitness has been a topic of hot debate in human evolution, with recent full genome sequencing efforts completed to look for candidate genes necessary for low oxygen adaptation. However, few have looked at the Sherpa population by sequencing their mitochondrial genomes---the powerhouse of every cell that helps determine the degree of respiratory fitness by providing 90 percent of the human body's energy demand, as well as controlling the metabolic rate and use of oxygen.

Unlike genomic DNA, the mitochondrial genome is unique inherited only through the mother, is small in size, and has a high mutation rate. Researchers Longli Kang, Li Jin et al. have sequenced 76 Sherpa individuals' complete mitochondrial genomes living in Zhangmu Town, Tibet, and found two mutations that were specific to the Sherpa population. The authors suggest that variants for one recent mutation in particular that was introduced into the Sherpa population about 1,500 years ago, A4e3a, that may be an important adaptation for low oxygen environments, or hypoxic conditions. This mutation is found in an "entry enzyme" stage in the mitochondrial respiratory complex, which may explain the importance of the role of mitochondria in the Sherpa population's ability to adapt to the extreme Himalayan environment.

The authors also shed light on the demographic history of Sherpa population size over evolutionary time, showing a significant expansion from 3,000 to 23,000 around 50,000 years ago, followed by a very recent bottleneck in the past several hundred years that reduced the population from 10,000 to 2,400, matching known historical migration patterns.

Media source:

Prof. Li Jin
Lijin.fudan@gmail.comMinistry of Education Key Laboratory of Contemporary Anthropology and Center for
Evolutionary Biology,
School of Life Sciences and Institutes of Biomedical Sciences,
Fudan University, Shanghai, China.

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